Rethinking Antimicrobials: Protecting the Microbiome in Clinical Practice with Dr. Brad Leech, PhD

Welcome to The Perfect Stool: Understanding and Healing the Gut Microbiome. This is your host, Lindsey Parsons. Today I'll be speaking with Dr. Brad Leach, a PhD clinical nutritionist and herbalist working out of the Sunshine Coast in Australia, renowned for his expertise in addressing chronic autoimmune conditions and complex gastrointestinal disorders. After entering the profession in 2008, Brad has contributed significantly to academia, shaping curricula at universities and delving into research areas such as intestinal permeability, autoimmune disease management, and the therapeutic potential of food-based probiotics. Brad is currently an adjunct fellow at the National Center for Naturopathic Medicine, where he continues to advance natural health sciences. Over the years, he has mentored thousands of practitioners, providing them with the tools to navigate the complexities of gut health. His program, Brad's Brainiacs Microbiome Mentoring, is a 6 month online mentorship designed to bridge the gap between cutting-edge research and real-world application. But before our conversation, if you haven't yet followed or subscribed to the show, be sure to do so. And if you want to get transcripts of the podcast, pop over to my website, HighDesertHealthCoaching.com, and sign up for my newsletter. You'll also get my free ebook, Finding Your Root Cause Through Stool and Organic Acids Testing, when you sign up. And if you haven't yet done my quiz on which stool or functional medicine test would help you get to your root cause, you can find a link in the show notes and take that. Now on to the show.

Welcome to the podcast, Bren.

Lindsey, it's great to be here.

I'm so excited to have you here.

I've been looking forward to this conversation.

Yes. And I'm sure we're going to deep dive into a number of different topics in relation to the microbiome and gut health and everything in between.

Yes. We talked about focusing on antimicrobials. So I want to start by asking you about what not to do, which is to say the most common antimicrobial herbs that are used traditionally for gut healing and issues that are harmful to the gut microbiome and what the research says about that.

Yeah. So this is an interesting one, and we need to consider that over the years, the way we evaluate the impact on the microbiome, the way we evaluate the effectiveness of herbal medicine has changed because we've changed the way that we sequence the microbiome. We've gone from culture to shotgun metagenomics. So our understanding of this whole ecosystem in the gut has shifted hugely in the last, especially 15 years, but more so the last 30 years. Now, historically, and I've got a background in herbal medicine and I love my herbs and I use herbs day in, day out with my patients, but something I started to notice 5+ years ago is this overprescription of antimicrobials, this, um, prescription whereby it wasn't just practitioners prescribing high-dose antimicrobials. It was— and I'm speaking from the viewpoint of the Australian market— consumers would just go into a pharmacy, a health food shop, and they would get over-the-counter, um, high-dose berberine, high-dose oregano oil, and were using it for things, yes, related to the microbiome, but also metabolic health or bloating or anything in between. And I was getting patients upon patients where you'd look at their microbiome report and it was shocking. There would be a reduction in diversity, there would be a changes to these beneficial species. And at that time, going into the literature, it was like, well, there's only indications to say that these herbal products were beneficial. There was culture and PCR-related studies to show that when you took berberine or oregano, and forget, forgive me for pronouncing it in the Australian way, how do you say it in America?

Oregano.

Oregano. There we go. My apologies. The limitations in the research were huge because they were saying it was a good thing. These high-dose antimicrobials were a good thing. But it wasn't until two studies that came out in 2020 and 2021. Now, these two studies, one by Zheng et al. and the other one by Ming et al., 2021, they were the first two studies which actually utilized metagenomic sequencing to measure the microbiome in herbal medicine intervention studies. Um, now for those, uh, listeners who might go, hold on, what's metagenomics? What's shotgun metagenomics? Very briefly, there are different ways to measure the microbiome. You've got culture, which is basically growing the microbes. You've got PCR, which is looking for a specific microbe with a probe. You have 16S, which is accurate down to the genus level, not so much to the species level. And then you've got shotgun metagenomics, which can look down to the species level to understand what species are changed.

And to the strain level at that.

Not, not the strain level. We're not there yet. So it's just down to the species level. To get down to the strain levels, we need something called nanopore technology, which is basically just you crack open the microbes and you pour out the full strain of the DNA to get access to it. They're utilizing this in some research settings. We are 15+ years away before we can look down at the strain level, but species, we're there and we should be looking at the species. So these two studies, they really jumped out at me when I was doing a bit of a deep dive, um, um, in and around the time that they were published around 2021. Because they utilize this metagenomic sequencing. So broadly speaking, these two studies, they were well-conducted studies, multicenter, uh, double-blind randomized control trials where they had around that 300 to 400 participants who were, um, one group were diabetic, the other group were hypoglycemic patients, and they prescribed anywhere between 500 to 600 milligrams of berberine twice daily for 12 to 16 weeks. So this is definitely a higher dose of berberine than what many practitioners would prescribe, but it is at the dose that you can buy over the counter. There are many, many supplements on the internet where it's around that 500 milligrams of berberine. And so they measured the microbiome.

And, and certainly those recommended for like, you know, people with type 2 diabetes.

Exactly. It's very effective when it comes around to high cholesterol, type 2 diabetes. But we as functional medicine doctors and naturopaths and everyone in between, we have this concept of first do no harm. So the interventions that we prescribe first and foremost shouldn't be causing any harm to the patient. So, and I'm going to tell you in a moment, the negative impact that these studies actually showed. So after the 12 to 16 weeks of around that 500 to 600 milligrams of berberine twice daily, what actually showed in the microbiomes were an increase in hexa-LPS-producing species. So LPS, your lipopolysaccharides, and we've got this subgroup of lipopolysaccharides called hexa-LPS, and they are the pro-inflammatory microbes. So taking high-dose berberine resulted in hexa-LPS increasing. But the other thing that was found were particular species that were linked up with disease outcomes. So Klebsiella pneumoniae, E. coli actually increased, which was like, we, we weren't expecting that. And then the plot thickens whereby these high-dose antimicrobials, and this is something that I've been seeing in practice for years now. They actually were shown in the research studies to reduce butyrate and commensals within the microbiome, including a lot of your Bifidobacteriums, in addition to reducing diversity within the microbiome. So, you know, thinking about that for a moment, we're taking an intervention that shifts the microbiome to a more negative state, a way that is more resembling disease outcomes rather than health. So I, I now question when we utilize antimicrobials, and that's to say that we, we should use antimicrobials, but we should use them based on the microbiome and we should use them in particular clinical situations and we should be utilizing more selective antimicrobials.

And so were there also studies on oregano?

Not oregano. I just said oregano. Not oregano. There are in vitro and animal-based studies showing positive impacts. And so we can only speak to berberine, but they have very similar actions antimicrobials. What I'd note with berberine is the actual herb, so using it in the cooking, amazing, lovely. But when we actually use the oil of oregano, it's much stronger. So it's much stronger to the microbiome and has a non-selective action, meaning that could actually impact the good and the bad. So when selecting antimicrobials, going for the extracts or maybe the tinctures and utilizing something called pulse dosing. So we might use one week on, one week off, or two weeks on, one week off. Other antimicrobials that we may consider to utilize may be Nigella or black cumin. Uh, pomegranate husk extract is an excellent one. And even garlic have been shown to be a bit more gentle but still effective as antimicrobials.

What about uva ursi, any?

Which one was that?

Uva ursi.

I'm not sure.

I don't know. It's just one of the ones that's commonly listed when you see that. If you, the old tests with the culture, they often would list what's the sensitivity for these antimicrobials and they, they always put berberine. I think oregano, garlic, and uva ursi on the list. Yeah.

I, I can't speak to that one. I haven't looked into it, unfortunately.

Okay. That's fine. And then other plant oils like thyme or cinnamon, are those also sort of along the same thing considered very strong?

Those, it's the oils. When it's the, the oils, it's a much stronger antimicrobial. And in some situation when there is a true pathogenic infection, yes, we may utilize it for a true pathogenic infection, but what a lot of practitioners utilizing it for are pathobionts. So pathobionts are things like, uh, M. smithii, Klebsiella pneumoniae, B. withuadia, um, E. coli, things that aren't causative of disease but associated with disease. Antimicrobials can safely be used for when it's a pathogen. And when I refer to it as a pathogen, I'm referring to things like Fali belly, Delhi belly, food poisoning, where there's quite obvious loose stools, abdominal discomfort causing a pathogenic infection.

I'm laughing because in Australia, you're the, maybe the closest place where people frequently get food poisoning is India. In the US, we call it Montezuma's Revenge because the closest place is Mexico where people often get food poisoning.

I love that one. I might use that in future.

Yeah. So yeah, so, so basically if you go get open parasites test at the doctor, that list of the really bad ones like Campylobacter or Salmonella, or, you know, these kinds of things that are the very pathogenic E. coli, C. diff, like these, this list of things.

Exactly. Exactly. So, I mean, it really depends. And I know the healthcare system in America is, is not one to, to rave about, but in some situations when it's quite acute loose stools in Australia, that's a referral to the GP. Go to the GP, get your antibiotics. But if there are lack of clinical symptoms, but these pathogenic infections are still identified, so they're suboptimal, that's when we can really come in with the antimicrobials. The other thing that I might stress here is at the same time of eliminating the infection, we want to protect the microbiome. So there's things that we can do to protect this ecosystem, one of which are going to be your HMOs, so your human milk oligosaccharides, a type of prebiotic first isolated from breast milk, and it's there to, to feed up the microbiome. Now, the research on HMOs show that it exclusively feeds the beneficial species while reducing the adhesion of pathogenic bacteria to the lining of the intestines. So it brings up this environment in the gut. Dosage-wise, you're looking around that 2 grams of the HMOs a day, per day. In some cases you could do 2 grams twice a day, but the thing to note is HMOs are very expensive, so that, that adds up very, very quickly.

Yeah.

The other one that we may utilize is your SB, so your Saccharomyces boulardii. Fantastic. Around that 200 milligrams a day. And then we've got a probiotic strain called Bifidobacterium lactis BB12, and that's been shown to survive and be still effective during antimicrobial and antibiotic use. So it's one that we can take alongside the stronger antimicrobials.

So I don't know if you've heard of the whole protocol involving MSM. Yeah, as an antimicrobial. Any sense of that and how potentially—

What I can say is there are many antimicrobials out there. Resveratrol on the outside of, of grapes is an antimicrobial. Turmeric is an antimicrobial. Their, their secondary actions can be antimicrobials. MSM is not one that I would typically think of as an antimicrobial, but there are many lower dose or, or weaker antimicrobials. We've just really got to consider when utilizing antimicrobials, are they impacting the species that we want them to impact? Or are they actually damaging the beneficial species? And unless we have research to confirm that, I'm always a bit cautious to go, I would rather cause less harm than more harm to the microbiome.

Yeah, no, I, uh, I, I asked because I had heard about on Neurology Jacoby's podcast, there was a, a doctor who came on and her, her protocol for everyone was MSM, work your way up to 32 grams. A day, and once you hit that level, usually the bloating's gone, everything's fixes. She doesn't even test the gut. So I, I, I'm like, okay, I'm not gonna recommend this protocol, but I'm gonna try it on myself.

And how did it go?

So I, because I, I have post-infectious IBS, so I just, I'm, I'm a great test case for whatever because whatever I have, it's always coming back. Like I can knock everything out and it's coming back. So, so I did, and I mean, it was great. Like like every other antimicrobial regime, it knocked out everything. And, and I was great. I didn't bloat for like, you know, maybe a week or something, and then everything started coming back. So I just started taking a little bit every day. So I've been holding off on a stool test to see whether it's decimated my good microbes or not, because I'm kind of at the point where, so when you have post-infectious IBS, you know that probably what's overgrowing is gonna be something that's LPS producing, right? So I'm thinking better for me to just kill stuff than to just continue to let this inflammation potentially, you know, hover in my body.

You raise a really good point here. Those studies that I showed— described just before, they are in a clinical setting where participants did nothing else other than take high-dose antimicrobials. I know for myself in my clinical practice, I never just prescribe one thing. I am recommending a variety of different supplements. I'm recommending a change in the diet and the lifestyle. And I've, I've spoken to a number of practitioners in this area, and they would utilize higher dose antimicrobials for SIBO management, but they would also alongside it give the PHGG and the kiwi fruit and no stacking. And they'll do these interventions that would actually have a positive effect on the microbiome. Along with prescribing these things like the HMOs, the SB, the B12 to protect the microbiome. And then thereby what they see in their practice is less of a negative impact to the microbiome. So yes, this study is, is, it's a very sterile study in the sense of it is just looking at one specific aspect. And in clinical practice, that's not really how we work, but it does illustrate the potential power of these herbs. They are very strong. They're very potent and we need to utilize them in the right place.

Okay.

So let's dig in a little bit more on the ones you did mention, how you use in particular the Nigella. Is that the, uh, the black cumin seed oil or black cumin?

Yes. Yeah. So Nigella, very gentle antimicrobial. I'd be utilizing a combination of the Nigella, the pomegranate husk extract, and even the garlic. When there is a pathogenic infection. When there's a pathogenic infection, I'd be utilizing a combination of antimicrobials whereby if it was, let's say, an overgrowth of a pathobiont, which was really impacting the microbiome. So let's say particular E. coli flexinarii was dominating the microbiome about that 5%, 20% type of, type of picture, like, you know, really dominating the microbiome. I would then utilize pomegranate husk extract as a, a gentle antimicrobial alongside, and you'll find this very interesting, an effective way to reduce E. coli in the bowel is actually with GOS. So your galactooligosaccharides. So GOS, it's a, it's a prebiotic. You can get it in, yes, food sources, but also as a supplement. Immunogoss is, is the GOS that has the research behind it that's used in a lot of these studies. And a dose range of around 4 grams per day. Per day has been shown after 12, 12 weeks to bring down E. coli species. Side note here, with GOS, you really want to go low, go slow, because if you jump in to, to 4 grams or 5 grams per day, you're going to get bloating. You know, it will really go, oof, because it's a FODMAP. It is a fermentable carbohydrate. It feeds up the microbes. So we want to slowly, slowly introduce it. There are definitely some individuals who can't tolerate GOS and who shouldn't be taking GOS, but those who can, it's a great tool to be utilizing to, to change the microbiome.

And we talked on the, on the pre-interview call about the MediHerb pomegranate husk extract. They have like the 3, what is it, 300 milligram pills. Well, it turns out it's not available in the US, but they're working on getting it available via Standard Process. So yeah, at this point, if you've ever tasted, probably haven't, pomegranate husk powder. It's perhaps one of the vilest things ever.

Okay.

Okay. I prefer to take it in a capsule.

It doesn't mix it in. I mean, you can mix it into a smoothie and hide it, but you're like, you're not gonna, you're not gonna put it in water. Like it's just going to sit there as a film on the top.

And then it's like, you know, it's not enjoyable and we need to, especially with compliance with patients, we need to have it in a way that's going to be easy for them to take.

Yeah.

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Yeah. And so how much of the Nigella do you use?

It really depends on the extract. I, I actually really like to use the seeds in the sense of in, in cooking. So you can get them from a, from an Indian shop and they bring out such an incredible flavor. In your cooking. The trick here is to actually put them in with like the onions at the beginning or in that first part of, of like a stir fry or in a curry. And it just extracts all of the flavor. And that's, that's one of the ways that I like to utilize the nigella.

Okay. So you're not talking about the oil then you're using the seeds?

No, not, not necessarily the oil. No.

Okay.

Yeah.

And would the cumin powder be, be just as good in that sense, or you want the seeds?

So black cumin and cumin are different. I imagine you can get black cumin. So that's like almost like the layman's term to describe it, but it's, it's similar to cumin, but different.

Okay.

I imagine you can get Nigella powder and you can get it in a capsule. And there are many supplements that have it in a capsule. And in, in some cases, yes, I would go for that.

Okay. Yeah. How about SBIs? Serum bovine immunoglobulins.

So your serum bovine colostrum?

Well, in, in this case it's the extracted immunoglobulins. I don't know if that's available in Australia at this point, but it's gotten a lot more popular in the US.

So what we have is we have got something called serum bovine colostrum. So it's a, it's a, it's a colostrum from the blood of, of cows, and it actually binds onto the byproducts of pathogens.

Right.

I think we're talking about the same thing. Right. Yes. Yes. Because it's dairy-free, it's from the plasma.

The thing with the serum bovine colostrum is it's really great when there is high levels of hexa-LPS within the microbiome. So when there are Klebsiella and E. coli in the microbiome, it does a great job at binding onto it. So the dose that I generally utilize is around that 2.5 grams, so around A head of a teaspoon and it's, it's quite potent. It's quite strong and effective as well.

Yeah, that's one of the supplements that I actually sell, but only in the US because it's too much of a pain to try and figure out how to export and all that. Yeah. And so, so when you, with the pomegranate husk pills, I guess the extract is, is somewhat different than the powder. I think it's more potent.

So we've got pomegranate husk extract. So that's the, the extract of the husk. And yes, it's, it is, it is much stronger compared to, and it's, it's very different to the actual pomegranate juice powder. Pomegranate juice powder isn't an antimicrobial. Pomegranate juice powder is a polyphenol, and it's actually going to feed up the microbiome, and it's actually going to increase akkermansia-based species as well. So really potent. I believe that the, um, like a 300-milligram capsule of the extract is equivalent to 3 grams of the husk. So it's it's about, you know, equivalent to almost a teaspoon.

So, yeah, no, the pomegranate powder and yeah. What other, what are poly, what other polyphenols do you recommend for building up those? If you use the GI Map, it was always like you go down the GI Map and like everything's looking good and zero Akkermansia, zero Faecalibacterium presence.

Yeah.

Those were always the two that were knocked out after people had done antibiotics or antimicrobials. So what, uh, what polyphenols or other, uh, prebiotics do you like to use to bring up?

The other thing to consider is with tests that utilize PCR, they're looking for just right, Akkermansia mucifilia. They're looking for just that one species whereby there are many, many other beneficial Akkermansia species, right, which may not be identified. So it's kind of giving that, that false indication as to Well, is there actually acromantia, or is there not? Or is there no acromantia muscifolia but acromantia others? Okay, so yes, I love the pomegranate. So I, I initially started doing actual pomegranate juice, so advising patients to, to consume pomegranate juice, but it was quite difficult to buy and source. And then you got the sugar content, and it was just the burden for the patient was too much. And then you can actually get frozen, like, pomegranate, like, you know, the little seeds in the pomegranate. You can get frozen pomegranate, and that's really nice to, to go onto a salad, to go into a smoothie, but accessing it is, is also an issue. So pomegranate juice powder is the way to go. It's, oh, it's a, it's an extract of the powder. It's very potent. You only need around that 250 milligrams of the extract of the powder. To be effective. It's an expensive product as well, but I love the aspect of, of the polyphenols feeding up the microbiome, especially when it comes around to those who may be unable to tolerate prebiotics. Polyphenols are an excellent option because they have these, these actions. And, and in fact, all polyphenols, they have 3 mechanisms of actions. They are anti-inflammatory, so they can reduce your CRP, interleukin 6, interleukin 8. They are also antioxidants, so they can support with that antioxidant aspect, and they're also antimicrobials. So we mentioned before that curcumin, resveratrol, quercetin can also be an antimicrobial, and even extract of green tea. So these, these polyphenols, they are incredible. So your grape seeds, your bilberry, your cranberries, aloe vera, pomegranate, as we mentioned, are all excellent polyphenols. Even curcumin, you know, we love curcumin as, as a polyphenol. The way that I like to get this into our patients is, is diet. Diet is going to be number one when it comes around to polyphenol prescription. We can take all the expensive polyphenol supplements we like., but we can get a huge amount in our diet. Couple of things I tell patients is diversity, diversity, diversity, and not just diversity in the foods, but diversity in the color. We want to have 5 different colors on our plate in each and every meal. Okay. Next one is going to be berries. Incorporate berries every single day. The amount of berries that we actually need to be therapeutic is around that 200 grams. So I don't know what that is in ounces, but it's about a punnet. Of, of blueberries is the general— a day. Yes, expensive, but frozen is perfectly fine. So you can get frozen and they need to be organic because the, um, the herbicides and pesticides they use in the berries will actually reduce the polyphenol content. Other one here is, is rather than using sauces in cooking, is to actually use your herbs and spices per, per gram, per teaspoon. Herbs and spices have got the highest amount of polyphenol compared to all other foods.

Yep.

Other ones here are switching from other oils. So whether it's vegetable oil, canola oils, butters, and so forth to olive oil, olive oil will have higher amounts of polyphenols. Switching a, I mean, yes, coffee will have polyphenols, but even incorporating things like green tea, there's, there's studies to show that 2 cups of green tea is significant enough, and this is high-quality green tea as well, is significant enough to bring down intestinal inflammation.

Yep.

Flaxseeds are another great polyphenol. Uh, grind them up, uh, adding them into a smoothie, adding them into oats are a great way to, to bring in a more fiber, but then more polyphenols.

And then I think lastly, it's, yeah, and some amount of conversion to, uh, to EPA and Exactly. Yeah.

And then the last one I might add in there would be chocolate. We can't go without chocolate. It is an excellent polyphenol, but no, there is no polyphenols in white chocolate or very little. We need to go for that, that dark chocolate. I was at my, um, my mother-in-law's last night and I looked in the fridge and she has 100% cacao and I was just like, that is incredible. And I tasted it and it's so incredibly bitter. I'm only at about that 85% cacao. That's, that's my threshold. My wife loves 90% cacao, but 100% cacao, if you can handle it, fantastic.

Yeah, I'm, I'm sort of at 70. That's kind of my max. So you mentioned in the list of polyphenols, grape seeds, and I, I always think of grape seed extract as a super strong, like, you know, could wipe out your microbiome kind of thing.

And that's the thing. Yes, it can be a stronger antimicrobial. When it comes around to the grapeseed, yes, it does have antioxidant capacity. Yes, it's anti-inflammatory, but it's also going to be antimicrobial as well.

So when you do pulse the stronger things, so I guess let me back this up a little bit and say that I often see people who, you know, you've tried the SPIs, you've tried the lighter stuff, you've kind of You know, and they're not getting better. Like they're miserable, they're bloated. They're just, they're just like a really, I, and they're, and they're going, they're saying, can I just get oregano oil? Like I just, you know, I, I saw that it's good for this, or can I just get this berberine or whatever? You know what I'm saying? They're, they're, they're coming at you with, they wanna take something stronger. So, so you feel like at this point you've tried the lighter stuff, you have to do something. Mm-hmm. So then you do try and you do try and pulse, but then sometimes I see this, there's a regression in the week off and it's like they lost, they lost some, uh, I don't know. And then, and then it seems like it never quite is as effective after you've, after you've pulsed. Have you experienced that at all?

In some situations, yes. And that's when I'd probably do like the 2 weeks, then 1 week off. But it's still that, that aspect where let's take, take SIBO. When we use antibiotics to treat SIBO, 40 to 60% of the time, within 6 months, it's going to come back. Uh, so it's not necessarily the, the, the answer. It's going to resolve it short term, but it's not getting to that underlying cause. So we've, we've got to consider, okay, if we're going to be utilizing these antimicrobials, how can we ensure that the patient doesn't come back to see us in 6 months' time with the exact same picture? And then we need to do it all over again, you know, more antimicrobials, more antimicrobials. And, and yes, In essence, antimicrobial herbs are going to be better for the microbiome than antibiotics. But we, yeah, we've, we've, we've got to be cautious here. And so that's why protecting the microbiome at the same time, lifestyle factors, cleaning up their diet, having that synergistic action whereby you, you do everything that they've tried before, but at the same time, you know, your stress management, you're not eating too late at night, you're, you're eating easy to digest foods. And then you bring in the antimicrobials and, and hoping that that's going to have a more sustained effect.

Mm-hmm.

And do you have testing in Australia for vinculin antibodies?

Which antibodies are those?

Vinculin for the post-infectious IBS.

So we have ways to look for antibiotic-resistant genes, so we actually look at the microbes to see what what genes they are resistant to, and based on those genes— so there's, uh, 20, 30+ genes to go, oh, it's resistant to this type of antibiotic or that, this type of antimicrobial. So utilizing more the DNA aspect. The thing to consider is, is when we do these studies where we have the microbes and we apply the antimicrobials, which is done in a lot of research studies, that's just looking at the effect on that particular species, and it's, it's difficult to determine whether or not that same effect will occur when we consume it and it goes down into the gut with, let's say, biofilms and, and everything else that's happening within the gut. So it's, it's one of those things where we've gotta consider, yes, that could be effective on a piece of paper, but is it actually going to be effective in clinical practice?

Yeah, no, what I'm talking about is something different. This is, this is from Mark Pittman's work and the IBS Smart Test, but I'm guessing you can't access that in Australia, so it's probably not something that you guys are using.

I don't believe so.

No. Yeah.

Okay.

So what test do you like for analyzing the microbiome? Do you use breath testing at all or you use stool testing?

I'll utilize stool testing and I'll utilize shotgun metagenomics. So where it utilizes metagenomic sequencing to look at all the species in the microbiome. That's the test that I'm, I'm going for because when you've got that species level information, it gives you an indication as to what's going on. Let me give you an example. Have you ever seen a microbiome report where they've got Streptococcus or Streptococcus sp.?

Yeah.

Whereby you don't actually know what species it is. You just know, well, there's the genus of, of Streptococcus. Within the Streptococcus genus, we have Strep A. So Strep A is a true pathogen. We also have Streptococcus thermophilus. So Streptococcus thermophilus is found in yogurt and is a commensal. There's, there's really nothing wrong with having that Streptococcus in our microbiome. You also have Streptococcus salivaris. So an oral microbiome. So you're, you're identifying species in the micro— in the, in the oral microbiome in the stool. Now, when we identify down to the species level,, it will really govern treatment direction. So for Streptococcus thermophilus, we're not doing any treatment. That's fantastic. We don't need to treat that Streptococcus. Yep. When it's Streptococcus salivaris, we're not coming in with an antimicrobial. We're not trying to kill that. An increase in oral species in the microbiome is actually an indicator of lack of stomach acid. So we can actually utilize high levels of oral species when there's 4 or more oral species. In the microbiome, it can actually allude to that there's a lack of stomach acid. So they've done these research studies. Those taking PPIs, your proton pump inhibitors, had an increase in oral species in the stool because there wasn't sufficient stomach acid to break down these oral species. Now, that type of understanding of species-level data is only available with metagenomic sequencing. And that's why that would be my, my, my choice of testing. The other one here to consider is how we can go about supporting that stomach acid. Yes, we can come in with betaine hydrochloride, but we also need to consider, well, is it stress governed? Should we be supporting stress management? Are there particular herbs like ginger and gentian and, and black pepper to really support with bringing up that stomach acid. So I think, yes, to answer your question in a roundabout way with an example, I'm utilizing metagenomic sequencing in my practice.

And what companies operate in Australia that you can access?

There are, there's one company called Cobion by Microba, and they were founded out of the University of Queensland. So two researchers, Professor Jean and Professor Phil, they were actually the ones who first published research on metagenomic sequencing back in 2004. So yeah, Cobine by Microba are the ones that are available in both Australia and the United Kingdoms. So the UK, you can access that as well through a company called Invivo.

Oh, okay.

And is this something that people can order themselves or is this exclusively via practitioners?

Because the tests contain diagnostic markers, it contains markers like pathogenic infections, it contains calprotectin, lactoferrin markers for inflammatory bowel disease. It actually needs to be ordered through a practitioner.

Mm-hmm.

Um, but these tests are, you know, it's, it's the gold standard for measuring the microbiome in Australia. So any practitioner who is educated in the microbiome, that's their preferred method of testing.

Yeah. So you mentioned seeing the Streptococcus salivarius. What other commensals from the mouth or pathogens from the mouth might you see that, that clue you into low stomach acid?

There are over 450 species which can be identified in the stool. Would you like me to name them all? I'm joking.

I, I, no, I just, I just thought there might be some common ones, like I can't name them all because there are so many.

A lot of Streptococcus. So a lot of Streptococcus. Streptococcus mutans will be one. There are a lot of Streptococcus. I actually can't recall all of them. I can't recall many of them purely because on metagenome sequencing tests, they have a little, almost like a button where it says the number of oral species. So they do all the calculations for you. So then you're not looking for, oh, which one's an oral species, which one's not. It would just say, there are 5 oral species and lists the oral species. And some of them are just weird and wonderful names, but they have been identified within the oral cavity.

Okay. Yeah, I, we don't have, well, at least not any of the ones I've been using. I've been using this one called the Tiny Health Pro because it's got the metagenomic sequencing plus all those markers, which is nice because most of the other metagenomic sequencing ones are just, just the sequencing. You just get the species. And I obviously, I want to see the markers too.

There is a database and I can't recall the name of it, but there is a database with all the oral species. So maybe there'll be a bit of manual handling on that one as well.

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You mentioned the ways to bring up stomach acid and, and yeah, I often get this situation where you have someone who just has persistently low stomach acid. Like they can take 5 betaine HCL at a meal, they feel nothing. And, and you know, their blood tests keep coming back with all sorts of markers of low stomach acid. So how do you, how do you address that? Like, you know, let's get into a little more detail on that.

And it really depends on the individual in front of us. Some of the options that I could utilize would be apple cider vinegar. It's simple, but it's effective. So apple—

what is it?

Apple cider vinegar.

Oh yeah.

Yep. So taking about a tablespoon in warm water with a meal, that's going to be acidic. My top herbs will be ginger, black pepper, and gentian. Yep. I don't utilize betaine hydrochloride. Frequently because it's just adding in the stomach acid. I would rather come at an approach of naturally stimulating it. So through those herbs and then also through vagus nerve stimulation. So stimulating the vagus nerve with bitters, but then also you can get different devices to stimulate the vagus nerve. Even singing, singing from high pitch to low pitch can stimulate the vagus nerve, chanting.

OM.

So that OM, that vibration can stimulate the vagus nerve. I, um, I was in India a number of years ago and you see these monks and so forth, you know, that they're, they're almost, they're on the side of the road drinking chai tea. Now in the chai tea has got more sugar than humanly possible. Like it is, it's basically tablespoons upon tablespoons of sugar. And I'm like, how are you living to 100 years of age when you eat so much sugar? And I put it down to they chant OM. For hours a day, stimulating the vagus nerve, bringing up stomach acid, and regulating inflammation. And I wonder, if we all just chanted Om for hours per day, could we eat more sugar? Maybe. Who knows? Other ones, other ones here are going to be hypnotherapy. So we can utilize something called gut hypnotherapy. Now, gut hypnotherapy is a, it's a process whereby you reconnect this bi-directional link between the mind and the gut, really effective for visceral hypersensitivity, IBS. And in fact, there's been a study, a multi-center study from Australia, the US, and the UK, where they compared gut hypnotherapy with a low FODMAP diet in IBS patients, and they found that the gut hypnotherapy was more effective short-term and long-term than the low FODMAP diet in IBS patients. So it's one of those things where rather than putting my IBS patients on a restricted low FODMAP diet, I'm actually leaning towards gut hypnotherapy. It's a 6-week program to reconnect this, this link, and then also bring down this visual hypersensitivity and support with the symptoms of, of IBS. But where I'm going with that, that can also support with that stomach acid production. And then there are particular probiotics, Saccharomyces boulardii, L. rhamnosus, Rosselle, can be effective to bring down oral species in the microbiome. So it's, it's promoted as a product to change the ecosystem in the, in the mouth when there are high amounts of oral species causing dental problems.

Yeah.

Okay.

So you mentioned black pepper. Are you talking about like Piperine, like they add to the curcumin supplements?

That can be an option or even just black pepper. Yeah, both.

Just putting pepper at your foot.

Yeah. Yeah. But both can be an option here. So in traditional Ayurvedic medicine, you have pippali. Um, it's like a long pepper and it's slightly sweet, but in some of the products that I'm using, it is, it's just black pepper. Extract, very small amount, to stimulate that, those digestive secretions.

So back onto the testing, what do you think about the accuracy of markers for things like pancreatic enzymes or steatocrit or secretory IgA on the functional stool test?

I can tell you so much about this. So there's a couple of things to consider. Pancreatic elastase, it is well known within the published literature that The accuracy to diagnose pancreatic insufficiency is extremely poor. Yep. Uh, the sensitivity specificity for identifying pancreatic insufficiency, it's quite terrible. And there are article upon article stating the exact same thing. So it's, it's when it becomes really, really, really low. And what's the reference range that you're using in the US?

So a lot of the markers will put 200 at normal, but But sort of generally we think of 500 as, even though that's further up, that that's really the more optimal? That's what we're thinking about.

It's, so similar ranges here in Australia. Anything above 200 is okay. Anything below 200 is indicating pancreatic insufficiency, but really to, to accurately diagnose pancreatic insufficiency correctly, it's more like below 50. Now that's just what I'm seeing within clinical practice. The literature is saying below 100, but it's in that range between 100 and 200 where it's not definitive. In saying that, I will always provide a digestive enzyme and stomach acid support and bitters to support that, and I see that that marker does increase, but it's once it goes down below that 50 mark, that's when I'm referring on to the GP to actually do further assessment for true pancreatic insufficiency. Which requires lifelong medication of digestive enzymes, not the digestive enzymes that naturopaths can access. I'm talking strong pharmaceutical-grade digestive enzymes.

Right. Yeah. The hardcore ones. And, and what if it's sort of in that middle range? Like it's, you know, it's 250, it's 300 or something.

Because of the test being less sensitive when it's above that 200 mark, you say that it's okay and you also go off clinical symptoms.

Yeah.

What was the other one you said? Secretory IgA?

Oh, secretory IgA. Yeah.

Yes. So the thing with secretory IgA is it is very sensitive to temperature and heat. Now, I've been involved in a number of lab comparisons where we've sent one sample. So we, we had an individual provide us a stool and from that one stool, we've sent it off to multiple different labs. In Australia, in the US, and compared the results. Very, very interesting, uh, in the sense of the results. One of the things that came back were secretory IgA and what it actually appears, and, and the literature confirms this as well, and the labs know this as well, is secretory IgA, which is exposed to high temperature or is not processed in a timely manner, can start to break down. So what can actually happen is low-quality labs will be reporting low secretory IgA more frequently than labs that have a higher duty of care and a higher standards. So I know growing up doing my, my degrees, it was always low secretory IgA. That was always going to be the issue, but that's because at that point in time, back in 2008, the labs were pretty poor and it was just, it was actually secretory IgA breaking down in the post. But here in Australia, especially in Queensland, there's, there can be heat waves, really hot temperature. And so ensuring that you've got the ice bricks and temperature control to ensure that it is getting back to the lab in a timely manner. So SecridiRGA, it is accurate as long as it is back to the lab in a timely manner. So generally within 48 hours, 72 hours, anything more than 72 hours is, is really gonna start to be broken down, and also don't want it to be exposed to high degrees of temperature. So you actually want a temperature control method in the parcel that you send back to the lab to ensure that it doesn't go above that threshold where it starts to break down.

Right. Right.

Okay.

Are the results of the study you were talking about where you sent it off to different labs public?

That was for some education programs that I put together where I wanted to compare different labs and and we go through that. It was a really interesting exercise comparing all these different labs. What I can say is it's very difficult to compare because different labs will call species by different names. They will give by different measurements as well. So they'll use different databases to name different bacteria. So broadly speaking, we have a number of different databases. We have a database called the GTDB. Which is the gold standard for naming microbes. So that's based on DNA. So that's the GTDB database. But a lot of research studies and a lot of older labs will utilize a database called the NCBI. Now, the NCBI database, it is completely inaccurate when it comes around to naming families and, uh, genuses and species in the microbiome. It just gives it completely different names. Because it's, it's an old, it's the older version of naming microbes. So, you know, there is this change in recent years on, on how we name microbes. The microbe in themself isn't changing, but the name that we provide it is changing because we're naming it based on the DNA rather than looking down a microscope and going, oh, this is producing X compound, it's a Lactobacillus. So we're, we're, we're changing how we name these species.

So I'm curious though, with the labs in the US, was there one that sort of came out like, this is the best one, or?

I don't want to negatively put down labs. What I would, what I'd illustrate—

that's why I just asked for the best. I didn't want to ask for the worst.

What I would illustrate is any lab utilizing metagenomics, shotgun metagenomics, fantastic, great. Any lab that's utilizing PCR. I'm sorry, we're, we're, we're so far past that. We don't just want a list of, hey, here are the, the 30, 40 species that we can identify. Are they in your gut? Yes or no. That is not microbiome assessment. That is just looking for a few key species. We want to be looking at the whole microbiome rather than just a subset of a few species, which that particular lab can measure.

Yeah, I have, as I've started to use metagenomic sequencing more and more, I've begun to realize that I was sort of operating in the dark when I was not using it because there were definitely species that were coming up that were just not on the list, you know? Oh, and even, you know, with hydrogen sulfide SIBO too, I'm seeing that there's some species that are not on, like one report has these three, but not all four or, you know, or even more. So it's not, it's not ideal, but sometimes you can't always have the ideal.

It's interesting. I get, I, I get patients, you know, Australia, UK, America, you know, they, they, they come to me and they, they have, um, microbiome results. And, and generally the US market, very interesting patients that come from the US. They've done so many different tests. Okay. And they've, they've probably done 4 different microbiome tests with 4 different companies, and I'll actually say, I'm actually not going to look at those results. I'm only going to look at the results using metagenomics because, well, A, I understand, you know, that the accuracy, and I don't want— there's this concept called identification bias. Identification bias is whereby if we see something that is positive, we believe that that's the problem.. So for instance, if we identify streptococcus or if we identify blastocystis, or if we, if we identify something and everything else is okay, we believe that that's the problem. And what's happening, especially here in, in, in Australia, GPs are going, yes, oh, the microbiome, but they're just doing really standard gut tests and it's not giving all the solutions. And they're just, they're identifying one marker and treating that one marker. Rather than really considering what else could be happening in the whole microbiome.

Yeah.

So new topic as we sort of get to towards the end. How do you think about leaky gut? Is this a condition in and of itself or secondary to other issues?

Yep. So background, my PhD was on leaky gut. I spent the better part of, of 5 years reading every single article on, on intestinal permeability. What I can say here is intestinal permeability, it isn't— it is not syndrome, it is not a condition, it is not a syndrome, it is a reaction. Okay, it's a reaction that can occur within the gut. So that disassembling of tight junctions within the small intestines, is it everything or is it a driving factor? I believe it's a driving factor rather than the sole focus that we as practitioners need to give it. Many things can drive up intestinal permeability, particular medications, microbes in the gut. Stress can be a massive one. And I used to say gluten, I used to say gluten was a driving factor for leaky gut, but the research actually has come out to say no, it's not a independent driving factor for leaky guts. And I know many people would be like, hold on, what are you saying here? And even colleague of mine, Dr. Fasano, who discovered zonulin, is in agreeance with this, whereby in the early days we did these studies with cell line where we had individuals with celiac disease, non-celiac gluten sensitivity, Crohn's disease, and healthy individuals, and we added a bit of gluten to all of these cell lines and permeability increased. But now we've got actual clinical studies where we had individuals and we gave them gluten to determine whether or not that resulted in permeability, and it didn't always increase permeability. There's a few exceptions to the rules. It appears that there's this threshold with the amount that you can tolerate. So it's about equivalent to a tablespoon or two of gluten. So that's not of gluten products, but of actual gluten. So around that 15 to 18 grams of actual gluten, which is about 2 pieces of toast.

Yeah.

But those with the celiac genes had greater permeability, even if they didn't have celiac. So, you know, I'm always looking for those celiac genes and recommending gluten-free in that case. There are some conditions like Hashimoto's. Inflammatory bowel disease, non-Celiac gluten sensitivities, and many others where I'd be advising gluten-free diet. But what I do focus on is when you eat gluten and you have clinical symptoms, why is it the fructans? Is it the glyphosates? Is it what else is going on in that product that is driving up those clinical symptoms? And the goal in some of my patients is to actually bring grains back. And I know, you know, for, for years we're saying grains are the devil, but I guarantee if you look at someone's microbiome who's avoiding all grains, it is a terrible microbiome. It is, it is a starving microbiome. It's got really high mucin-degrading species in the gut because there's not enough fiber in the diet. Very difficult to get enough fiber purely from, from vegetables. So we need to be considering grains. They could be gluten-free grains, by all means, or they could be gluten-containing grains. But I just, I thought I'd throw that out there as a bit of a, a novel approach around leaky gut.

Yeah. So how are you diagnosing the non-celiac gluten sensitivity then?

Well, that would be through clinical symptoms, but then we also will utilize particular pathology in the bowel. So we'd utilize stool zonulin as a marker for permeability. Along with hexa-LPS and butyrate as indications for that bowel integrity. I'll also utilize hydrogen sulfide producing species to indicate whether or not there's permeability as well.

What is the relationship between the hydrogen sulfide ones and permeability?

So hydrogen sulfide, the, the research shows that it can actually break apart those mucin bonds in the gut, and it can actually be a driving factor behind the intestinal permeability.

Oh, okay. Yeah. So I used to be gluten-free and because I had Hashimoto's, but I, I completely reversed that. My antibodies have been at zero and finally I'm just like slowly but surely more and more gluten back into my diet and I'm just like, am I killing myself here? But I feel like I'm okay. You know what?

Monitor the antibodies just to ensure that they stay low.

Yeah, I did. I did like for 5 years, they, I was getting more and more gluten and still was staying zero. Still zero.

Yeah.

A little bit is fine. Especially if it's a sprouted gluten or a fermented sourdough, it's gonna be a lot easier to digest.

Yeah, it's fermented sourdough with like organic flour. It's like all the things.

Oh, fantastic. With some avocados, some poached eggs. Love it.

Yeah, exactly. Do we have time for one more question?

Go for it.

Okay. How do you seal up a leaky gut?

That is a great question. So part of my PhD, we published The Clinical Practice Guidelines for the Management of Intestinal Permeability, where we looked at over 22,000 research studies on the management of intestinal permeability. We evaluated them for their evidence, their risk of bias, their, their accuracy, and we narrowed down to our treatment recommendations. And you can download this, this full guide from our website free of charge. And it's got all of the recommendations that we have made to practitioners when it comes around to managing intestinal permeability in relation to, uh, when to, when to avoid gluten, when to consume gluten, probiotics, prebiotics, everything in between. What I would say are the top interventions based on the research, uh, it would be zinc, glutamine, and SB. And I know that's not new or novel to anyone, but they are the ones that have the highest amount of evidence to show that they are effective when it comes around to healing and sealing the gut.

Okay. So zinc carnosine or just any kind of zinc?

Zinc carnosine. Yes. Around that 25 milligrams.

And what is the dosing on the glutamine? 'Cause that's a, a subject of, of good controversy.

Now it's a, it's controversy as well. Most supplements do not contain enough glutamine. Generally speaking, it's around that 5 to 15 grams of glutamine per day. Now, most patients can tolerate 5 grams, no problems. I had a patient just this week email me to say that they, they had then gone to increase to 10 grams and their neurological issues started going through the roof. So we've got that issue with too much glutamine. It can go down that pathway. It can be neurostimulating and can actually cause anxiety, rapid heart rates, and other impacts like that. So yes, the research studies are actually saying 5 grams 3 times daily, but in a lot of patients it's difficult to get to that dose. If I really feel that it's needed, then I would be coming in with things like L-theanine, magnesium, or even NAC to counteract the negative impact of high-dose glutamine.

Okay. And you were talking about, uh, SD with Saccharomyces boulardii, right?

That's correct.

Right. Good. Okay. I find that that's one that just like a lot of times I'm just like, just, that's a good ongoing one. Like that's just a good probiotic to have, have as, you know, protection.

It's, it's protect, like if you're going overseas, great, take it. If you, you know, might need antibiotics, take it. It's, it's a great probiotic.

Yeah. It was, it was on my kind of list of stuff that I always took and So many other things found their way onto my list of things. I mean, I take 30 supplements a day because I'm just like a giant guinea pig for everything and everybody sends me free supplements. So anyway, it fell off the list and then, you know, started having like diarrhea and I'm like, what's going on? I'm like, I need to go get some Saccharomyces boulardii. What am I doing? Just go back with the old friends.

Great for loose stools.

Yeah.

What I have noticed in some individuals, and this only happens to about 10% is constipation. If you can take, if you take SB in some individuals, you can develop constipation.

Yeah.

Yeah. Okay. Well, this has been awesome. So much good information. I really appreciate your time and your knowledge and sharing it all with us.

It's been fantastic and I've, I've thoroughly enjoyed all the questions and all the topics we've discussed.

Awesome. Well, thank you so much.

This was an important conversation and I hope you all take it to heart. Like Brad, I see a lot of stool tests from clients who have taken lots of antibiotics or antimicrobial herbs prior to seeing me, and important keystone species that are health protective are missing from their microbiomes. And while more and more probiotics with these species are becoming available, there's no guarantee that they'll implant. So please don't just grab a strong antimicrobial herb like berberine or oregano oil casually and self-treat, because you may end up creating more of a mess of your microbiome and health than you started with. You can support the podcast by buying supplements at a discount from my FullScript Dispensary, ordering tests at a discount from my Rupa Health Labs store, or using my affiliate links to iHerb, which is available worldwide, or Amazon. And just note that you can use my Amazon link to buy anything, not just supplements, and support the podcast. And I see that there are definitely some of you doing that now, and I really wanted to say how much I appreciate it. In case anyone wondered, one does not get rich as a health coach, so any affiliate income that I can bring in from Amazon and other affiliate programs helps to support the podcast and the work I do with clients that is very time-consuming. So I'd love it and really appreciate it if you'd bookmark my link and use it for regular Amazon purchases. If you'd like to connect with me online, you can follow my High Desert Health Facebook page, join my Gut Healing Facebook group, or join my newsletter list at highdeserthealthcoaching.com, as well as follow me on X, Instagram, TikTok, and Pinterest. Links for those are in the show notes. Thanks for joining me today, and here's wishing you all the perfect stool.